Emricasan, a Caspase Inhibitor, for Treatment of Subjects With Decompensated NASH Cirrhosis

NCT ID: NCT03205345

Last Updated: 2019-03-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

210 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-28

Study Completion Date

2019-08-31

Brief Summary

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This is a multicenter, double-blind, randomized, placebo-controlled study to evaluate the safety and efficacy of emricasan in improving event-free survival based on a composite clinical endpoint (where all-cause mortality, new decompensation events, and MELD score progression are events) in subjects with decompensated NASH cirrhosis.

Detailed Description

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The study treatment duration will be at least 48 weeks with study visits every 4 weeks up to Week 48 and every 8 weeks after Week 48. All subjects will continue treatment until the last subject in the study reaches 48 weeks in the study. At least 30% of subjects randomized should have baseline MELD score ≥15 and ≤20.

For each subject, the study will consist of:

* Screening period of up to 4 weeks
* Randomized, double-blind treatment period of at least 48 weeks
* A follow-up visit 2 weeks after completion of study drug treatment

The duration of each subject's participation will be at least 54 weeks for those completing the entire study.

Conditions

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Decompensated Cirrhosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Study drug will be double-blind with matching placebo. Emricasan at 25 mg or 5 mg or matching placebo will be administered orally twice a day.

Study Groups

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Emricasan (25 mg)

Emricasan 25 mg

Group Type ACTIVE_COMPARATOR

Emricasan (25 mg)

Intervention Type DRUG

25 mg emricasan

Emricasan (5 mg)

Emricasan 5mg

Group Type ACTIVE_COMPARATOR

Emricasan (5 mg)

Intervention Type DRUG

5 mg emricasan

Placebo

Matching placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching Placebo

Interventions

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Emricasan (25 mg)

25 mg emricasan

Intervention Type DRUG

Emricasan (5 mg)

5 mg emricasan

Intervention Type DRUG

Placebo

Matching Placebo

Intervention Type DRUG

Other Intervention Names

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IDN-6556 IDN-6556 Matching placebo

Eligibility Criteria

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Inclusion Criteria

1. Male or female subjects 18 years or older, able to provide written informed consent and able to understand and willing to comply with the requirements of the study.
2. Cirrhosis due to NASH with exclusion of other causes of cirrhosis (e.g. chronic viral hepatitis, alcoholic liver disease, etc.)
3. At least one of the following: a) history of variceal hemorrhage (more than 3 months prior to day 1) documented on endoscopy and requiring blood transfusion, b) history of at least moderate ascites (on physical exam or imaging) currently treated with diuretics.
4. MELD score ≥12 and ≤20 during screening
5. Albumin ≥2.5 g/dL during screening
6. Serum creatinine ≤1.5 mg/dL during screening

Exclusion Criteria

1. Evidence of severe decompensation
2. Non-cirrhotic portal hypertension
3. Child-Pugh score ≥10
4. Current use of anticoagulants that affect prothrombin time or international normalized ratio
5. ALT \>3 times upper limit of normal (ULN) or AST \>5 times ULN during screening
6. Initiation or discontinuation of non-selective beta blockers within 1 month of screening
7. Transjugular intrahepatic portosystemic shunt or other porto-systemic bypass procedure within 1 year of screening or previously requiring revision
8. Alpha-fetoprotein \>50 ng/mL in the last year
9. History of hepatocellular carcinoma (HCC) or evidence of HCC
10. History of malignancies other than HCC, unless successfully treated with curative intent and believed to be cured
11. Prior liver transplant
12. Uncontrolled diabetes mellitus (HbA1c \>9%)
13. Change in diabetes medications or vitamin E within 3 months of screening
14. Restrictive bariatric surgery or bariatric device within 1 year of screening or prior malabsorptive bariatric surgery
15. Symptoms of biliary colic unless resolved following cholecystectomy
16. History of significant alcohol consumption within the past 5 years
17. Current use of medications that are considered inhibitors of organic anion transporting polypeptide OATP1B1 and OATP1B3 transporters
18. Prolongation of screening (pre-treatment) QTcF interval of \>500 msecs, or history or presence of clinically concerning cardiac arrhythmias
19. Significant systemic or major illness other than liver disease
20. Human immunodeficiency virus infection
21. Use of alcohol, controlled substances (including inhaled or injected drugs), or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Conatus Pharmaceuticals Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jean L Chan, MD

Role: STUDY_DIRECTOR

Conatus Pharmaceuticals Inc.

Locations

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The Institute for Liver Health

Chandler, Arizona, United States

Site Status

St. Joseph's Hospital & Medical Center

Phoenix, Arizona, United States

Site Status

Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

University of Arizona Liver Research Institute

Tucson, Arizona, United States

Site Status

University of California, San Francisco-Fresno

Fresno, California, United States

Site Status

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status

UCLA Pfleger Liver Institute

Los Angeles, California, United States

Site Status

California Liver Research Institute

Pasadena, California, United States

Site Status

Stanford University

Redwood City, California, United States

Site Status

Inland Empire Liver Foundation

Rialto, California, United States

Site Status

UC Davis GI/Hepatology Clinical Trials Unit

Sacramento, California, United States

Site Status

Scripps Clinic - Torrey Pines

San Diego, California, United States

Site Status

California Pacific Medical Center

San Francisco, California, United States

Site Status

University of California San Francisco

San Francisco, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

Peak Enterology Associates

Colorado Springs, Colorado, United States

Site Status

West Haven VA Medical Center

West Haven, Connecticut, United States

Site Status

UF Hepatology Research at CTRB

Gainesville, Florida, United States

Site Status

Mayo Clinic

Jacksonville, Florida, United States

Site Status

Florida Research Institute

Lakewood Rch, Florida, United States

Site Status

Schiff Center for Liver Disease/University of Miami

Miami, Florida, United States

Site Status

Florida Hospital Transplant Institute

Orlando, Florida, United States

Site Status

IMIC Inc.

Palmetto Bay, Florida, United States

Site Status

Tampa General Hospital

Tampa, Florida, United States

Site Status

Piedmont Transplant Institute

Atlanta, Georgia, United States

Site Status

Gastrointestinal Specialists of Georgia

Marietta, Georgia, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Aquiant Research

Albany, Indiana, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics/ Internal Medicine

Iowa City, Iowa, United States

Site Status

Delta Research Partners

Bastrop, Louisiana, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Walter Reed National Military Medical Center (WRNMMC)

Bethesda, Maryland, United States

Site Status

Digestive Disease Associates, PA

Catonsville, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

University of Mississippi Medical Center, Division of Digestive Diseases

Jackson, Mississippi, United States

Site Status

Kansas City Research Institute

Kansas City, Missouri, United States

Site Status

Rutgers New Jersey Medical School

Newark, New Jersey, United States

Site Status

Northwell Health Inc., Sandra Atlas Bass Center for Liver Diseases.

Manhasset, New York, United States

Site Status

NYU Medical Center

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Columbia University Medical Center - Center for Liver Disease and Transplantation

New York, New York, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Carolinas Healthcare System, Center for Liver Disease

Charlotte, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Diabetes & Endocrinology Consultants, PC

Morehead City, North Carolina, United States

Site Status

UC Health/ UCPC LLC

Cincinnati, Ohio, United States

Site Status

Options Health Research, LLC

Tulsa, Oklahoma, United States

Site Status

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

GHS Gastroenterology and Liver Center

Greenville, South Carolina, United States

Site Status

ClinSearch, LLC

Chattanooga, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Texas Clinical Research Institute

Arlington, Texas, United States

Site Status

Methodist Health System Clinical Research Institute

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor Scott & White Research Institute

Fort Worth, Texas, United States

Site Status

Baylor College of Medicine - Advanced Liver Therapies

Houston, Texas, United States

Site Status

Liver Associates of Texas, P.A.

Houston, Texas, United States

Site Status

American Research Corporation at the Texas Liver Institue

San Antonio, Texas, United States

Site Status

Methodist Specialty & Transplant Hospital

San Antonio, Texas, United States

Site Status

San Antonio Military Medical Center

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

Emeritas Research Group LLC

Leesburg, Virginia, United States

Site Status

Banner University Medical Center - Phoenix Transplant Institute

Newport News, Virginia, United States

Site Status

Bon Secours Liver Institute of Virginia

Richmond, Virginia, United States

Site Status

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status

Swedish Organ Transplant and Liver Center

Seattle, Washington, United States

Site Status

University of Washington Harborview Medical Center

Seattle, Washington, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Frenette C, Kayali Z, Mena E, Mantry PS, Lucas KJ, Neff G, Rodriguez M, Thuluvath PJ, Weinberg E, Bhandari BR, Robinson J, Wedick N, Chan JL, Hagerty DT, Kowdley KV; IDN-6556-17 Study Investigators. Emricasan to prevent new decompensation in patients with NASH-related decompensated cirrhosis. J Hepatol. 2021 Feb;74(2):274-282. doi: 10.1016/j.jhep.2020.09.029. Epub 2020 Oct 8.

Reference Type DERIVED
PMID: 33038432 (View on PubMed)

Other Identifiers

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IDN-6556-17

Identifier Type: -

Identifier Source: org_study_id

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